This invention relates to the measurement of dye concentrations in a living organism. More specifically, it relates to the optical measurement of the concentrations of an indicator dye in a living organism for the purpose of calculating physiological parameters such as cardiac output, blood flow and blood volume by analyzing the indicator concentration time curve (ICTC).
Cardiac output (CO), blood flow (BF) and blood volume (BV), are important physiological parameters for evaluating the functions of vital organs. Therefore, measurements of these parameters are routinely performed in clinical practice as well as in research. Indicator dilution technique is a method commonly used to calculate CO, BF and BV. Generally, a known amount of indicator, such as a dye, or cold saline bolus, is introduced into the circulation via right atrium or central vein. Several ICTCs are then measured downstream in different parts of the body. CO can be calculated from the amount of the indicator and the ICTC from arterial blood. BF and BV of a vital organ can be calculated by analyzing the ICTCs simultaneously obtained from said vital organ and from the arterial blood.
Optical technology has been widely used to obtain ICTCs invasively and non-invasively for measuring CO, BF and BV. For example, U.S. Pat. Nos.5,494,031 and 5,458,128 illustrate methods of calculating the concentrations of an indicator dye by utilizing the concentration of blood hemoglobin as a reference. However, these methods require light at least at two different wavelengths. Roberts I G, et al, (J Thorac Cardiovasc Surg 1998;1 15:94-102) has described a method of estimating cerebral blood flow and cerebral blood volume by simultaneously obtaining ICTCs of a dye (indocyanine green) from the arterial blood with a fiberoptic catheter and from the brain with a near infrared spectrometer. However, this method requires multiple wavelengths, which usually introduce a certain amount of error since the scattering of the light from the blood components and tissue are unequal at different wavelength.
An object of the present invention is to provide a new and improved apparatus and method for measuring ICTCs optically from the blood of a living organism using a single wavelength. Whereby, physiological parameters such as cardiac output, total blood volume and liver function can be calculated by analyzing the ICTCs.
It is another object of the present invention to provide a new and improved apparatus and method for measuring ICTCs optically from a vital organ using a single wavelength. Whereby, physiological parameters such as blood flow and blood volume of said vital organ could be calculated by analyzing the ICTCs simultaneously obtained both from the arterial blood and from said vital organ of the living organism. Further objects and advantages of the present invention will become apparent from a consideration of the drawings and ensuing description.
The foregoing objects and others are realized with the assumption that the blood oxygen saturation SO2 and particularly the concentration of blood hemoglobin Hb of the living organism do not change during the brief measurement period. Prior studies indicated that this assumption is reasonable and changes in the optical attenuation after the dye injection is caused only by the absorption of the indicator dye (Kuebler W M, et al, J of Cerebral Blood Flow and Metabolism 1998:445-456). Furthermore, it is also assumed that the values of Hb and SO2, which can be obtained using routine laboratory and oximetry methods, are available as references for calculating the concentrations of the indicator dye.
According to the present invention the methods of measuring ICTCs from the circulation, such as the arterial blood and from a vital organ, such as the brain of a living organism include: projecting light into the living organism; measuring optical density of the arterial blood I(0)a and optical density of the brain I(0)b at a single wavelength xcex before a predetermined initial time to establish the baseline values; introducing an indicator dye with known amount Q into the circulation via right atrium or central vein at the initial time; measuring optical density of the arterial blood I(t)a and optical density of the brain I(t)b after the initial time; measuring the concentration of blood hemoglobin Hb, blood oxygen saturation SO2 and mean optical pathlength; computing the concentrations of the indicator dye in the arterial blood Cd(t)a and in the brain Cd(t)b by comparing I(t)a and I(t)b with their initial baseline values I(0)a and I(0)b and by selectively utilizing the values of the Hb, the SO2 or the mean optical pathlength; and then obtaining the ICTCs by plotting Cd(t)a and Cd(t)b against time t.
In a practical application of the invention, the single wavelength xcex is chosen at around 800 nm. Indocyanine green (ICG), which has a maximum absorption at 800 nm, is used as the indicator dye. The optical density of the arterial blood can be obtained via a fiber optic catheter inserted into a radial artery, for example, or measured non-invasively using the arterial pulsatile signal similar to the method used by a pulse oximeter. Likewise, the optical density of the vital organs can be obtained via fiber optic probes attached to the cardiac muscle, for example, or measured from the brain non-invasively using a probe similar to the one used by a near infrared spectrometer.